The American Diabetes Association reports that approximately 6% of the population in the United States, a group of 16 million people, has diabetes, and that this number is growing at a rate of 12-15% per annum. The Association further reports that diabetes is the seventh leading cause of death in the United States, contributing to nearly 200,000 deaths per year. Diabetes is a life-threatening disease with broad complications, which include blindness, kidney disease, nerve disease, heart disease, amputation and stroke. Diabetes is believed to be the leading cause of new cases of blindness in individuals aging between 20 and 74; approximately 12,000-24,000 people per year lose their sight because of diabetes. Diabetes is also the leading cause of end-stage renal disease, accounting for nearly 40% of new cases. Nearly 60-70% of people with diabetes have mild to severe forms of diabetic nerve damage which, in severe forms, can lead to lower limb amputations. People with diabetes are 2-4 times more likely to have heart disease and to suffer strokes.
Diabetes results from the inability of the body to produce or properly use insulin, a hormone needed to convert sugar, starches, and the like into energy. Although the cause of diabetes is not completely understood, genetics, environmental factors, and viral causes have been partially identified.
There are two major types of diabetes: Type 1 and Type 2. Type 1 diabetes (also known as juvenile diabetes) is caused by an autoimmune process destroying the beta cells that secrete insulin in the pancreas. Type 1 diabetes most often occurs in young adults and children. People with Type 1 diabetes must take daily insulin injections to stay alive.
Type 2 diabetes is a metabolic disorder resulting from the body's inability to make enough, or properly to use, insulin. Type 2 diabetes is more common, accounting for 90-95% of diabetes. In the United States, Type 2 diabetes is nearing epidemic proportions, principally due to an increased number of older Americans and a greater prevalence of obesity and sedentary lifestyles.
Insulin, in simple terms, is the hormone that allows glucose to enter cells and feed them. In diabetics, glucose cannot enter the cells, so glucose builds up in the blood to toxic levels.
Diabetics having Type 1 diabetes are typically required to self-administer insulin using, e.g., a syringe or a pen with needle and cartridge. Continuous subcutaneous insulin infusion via external or implanted pumps is also available. Diabetics having Type 2 diabetes are typically treated with changes in diet and exercise, as well as with oral medications. Many Type 2 diabetics become insulin-dependent at later stages of the disease. Diabetics using insulin to help regulate their blood sugar levels are at an increased risk for medically-dangerous episodes of low blood sugar due to errors in insulin administration, or unanticipated changes in insulin absorption.
It is highly recommended by the medical profession that insulin-using patients practice self-monitoring of blood glucose (“SMBG”). Based upon the level of glucose in the blood, individuals may make insulin dosage adjustments before injection. Adjustments are necessary since blood glucose levels vary day to day for a variety of reasons, e.g., exercise, stress, rates of food absorption, types of food, hormonal changes (pregnancy, puberty, etc.) and the like. Despite the importance of SMBG, several studies have found that the proportion of individuals who self-monitor at least once a day significantly declines with age. This decrease is likely due simply to the fact that the typical, most widely used, method of SMBG involves obtaining blood from a capillary finger stick. Many patients consider obtaining blood to be significantly more painful than the self-administration of insulin.
Non- or minimally-invasive techniques are being investigated, some of which are beginning to focus on the measurement of glucose on the skin surface or in interstitial fluid. For example, U.S. Pat. No. 4,821,733 to Peck describes a process to detect an analyte that has come to the skin surface via diffusion. Specifically, Peck teaches a transdermal detection system for the detection of an analyte that migrates to the skin surface of a subject by diffusion in the absence of a liquid transport medium, such as sweat. As will be described in more detail below, because the process of passive diffusion of an analyte to the skin surface takes an unreasonably long period of time (e.g., a few hours to several days), Peck does not provide a practical non-invasive glucose monitoring solution.
Similarly, U.S. Pat. No. 6,503,198 to Aronowitz et al. (“Aronowitz”) describes a transdermal system for analyte extraction from interstitial fluid. Specifically, Aronowitz teaches patches containing wet and dry chemistry components. The wet component is used to form a gel layer for the extraction and liquid bridge transfer of the analyte from the biological fluid to the dry chemistry component. The dry chemistry component is used to quantitatively or qualitatively measure the analyte. One disadvantage of the system described in Aronowitz is the effect of a wet chemistry interface in providing a liquid phase environment on the skin in which different sources of glucose could be irreversibly mixed with one another. A liquid phase contact with the skin surface could make it impossible to distinguish between glucose on the skin surface originating from many day old epidermal debris, glucose on the skin surface originating from many hours old transdermal diffusion, and finally, glucose on the skin from the more timely output of the eccrine sweat gland.
Others have investigated glucose measurement in sweat; however, they have failed to demonstrate a correlation between blood glucose levels and sweat glucose levels, and have similarly failed to establish or demonstrate that only glucose coming from sweat is being measured. For example, U.S. Pat. No. 5,140,985 to Schroeder et al. (“Schroeder”) describes a non-invasive glucose monitoring unit, which uses a wick to absorb the sweat and electrochemistry to make glucose measurements. Schroeder relies on an article by T. C. Boysen, Shigeree Yanagaun, Fusaho Sato and Uingo Sato published in 1984 in the Journal of Applied Psychology to establish the correlation between blood glucose and sweat glucose levels, but quantitative analysis of the data provided therein demonstrates that the blood glucose and sweat glucose levels of the two subjects described there cannot be correlated (yielding correlation coefficients of approximately 0.666 and 0.217 respectively). Additional methods must be used, beyond those cited in the paper by Boysen et al., to isolate the glucose in sweat from other sources of glucose on the skin.
Similarly, U.S. Pat. No. 5,036,861 to Sembrowich et al. (“Sembrowich”) describes glucose monitoring technology based on analyzing glucose on the skin surface from a localized, modified sweat response. In a like manner, U.S. Pat. No. 5,638,815 to Schoendorfer (“Schoendorfer”) describes a dermal patch to be worn on the skin for increasing the concentration of an analyte expressed through the skin in perspiration, to a conveniently measurable level. However, similar to Schroeder, Sembrowich and Schoendorfer each fail to teach or describe methods or steps for isolating or distinguishing the glucose in sweat from other confounding sources of glucose found on the skin surface.